Objective: Endoscopic repair of cerebrospinal fluid (CSF) leaks has become a routine approach. This study describes endoscopic closure of a large series over 21 years, focusing on management, surgical technique, and long-term outcomes. Study Design: Chart review. Subjects and Methods: CSF leak patients treated by the senior author and at the University of Pennsylvania from 1987 to 2008. The data included body mass index (BMI), etiology, defect location, graft material, presence of encephalocele, lumbar drain, history of meningitis, intracranial pressure, recurrence, and follow-up. Results: A total of 193 cases were identified. Follow-up ranging from 1 month to 9 years (mean 21 months) was available on 166 patients. The etiology was spontaneous in 77 patients (40%), traumatic in 109 (56%), and congenital in 7 (4%). The average BMI of spontaneous CSF leak patients (35) was greater (P < 0.001) than both traumatic (30) and congenital patients (23). Defects were most commonly located in the sphenoid (n = 62, 32%) and ethmoid (n = 60, 31%) The initial success rate was 91 percent (n = 176) and overall success rate was 98 percent (n = 190). Conclusion: The overall success rate (98%) and low morbidity in this large series support endoscopic approach as standard of care for CSF leak closure. © 2009 American Academy of Otolaryngology-Head and Neck Surgery Foundation.